Introgen Therapeutics and the University of Texas MD Anderson Cancer Center (UTMDACC) are collaborating to develop a novel gene therapy approach for an important clinical disease, lung cancer. The collaboration will address three pre-clinical hypotheses. The first hypothesis is that Ad-mda7 will exhibit tumor specificity and kill lung tumor cells. This hypothesis is based on the demonstrated pro-apoptotic nature of Ad-mda7 in breast cancer cell lines. The second hypothesis is that Ad-mda7 apoptotic induction is through pathways distinct from those of the tumor suppressor p53. The basis for this hypothesis is the cytotoxic activity shown in p53 null cell lines in addition to inherent differences between p53, a transcription factor, and MDA7, a secreted molecule. The third hypothesis is that Ad-mda7 is an effective in vivo therapeutic when administered by intratumoral injection. This hypothesis is based upon prior experience with Ad-p53 and the translation of those pre-clinical results into animal models and ultimately, clinical trials. The long-term survival of lung cancer patients is significantly impacted by locoregional therapies. The results of the proposed studies will determine the potential of Ad-mda7 to improve locoregional control, thus improving the long-term survival of lung cancer patients. PROPOSED COMMERCIAL APPLICATIONS: According to the American Cancer Society there were an estimated 171,500 new cases of lung cancer in the USA in 1998. While lung cancer accounts for 14% of all cancers diagnosed, it is responsible for 28% of all cancer deaths. Despite advances in surgery, radiation therapy and chemotherapy, the overall 5 year survival rate in lung cancer is only 14% mandating the need for novel forms of therapy. The unique mechanism of mda-7 action would expand anti- cancer gene therapy options for lung cancer.